Tau Positron Emission Tomography (PET) Longitudinal Substudy Associated With: Study of Crenezumab Versus Placebo in Preclinical Presenilin1 (PSEN1) E280A Mutation Carriers in the Treatment of Autosomal-Dominant Alzheimer's Disease

Phase 2

Completed

Conditions: Alzheimer Disease

Interventions: Drug: Placebo
Drug: Crenezumab
Other: [^18F]GTP1

Registration Number: NCT03977584

Lead Sponsor: Hoffmann-La Roche

Brief Summary: This substudy will evaluate the effect of crenezumab on the longitudinal tau burden in a subgroup of preclinical Presenilin1 (PSEN1) E280A mutation carriers and non-carriers, who were enrolled in study NCT01998841 (GN28352). Participants will receive up to three intravenous (IV) injections of \[\^18F\] Genentech Tau Probe 1 (GTP1) and will undergo a tau positron emission tomography (PET) scan after each IV injection of \[18\^F\]GTP1. The purpose of this substudy is to increase the understanding of disease progression in the preclinical stage of familial Alzheimer's Disease (AD).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 114

Inclusion Criteria

Enrolled in main Study NCT01998841 (GN28352).

Exclusion Criteria

Contraindication to PET scan procedures, possibly including, but not limited to current, past, or planned participation in studies involving radioactive agents, including the main Study NCT01998841 (GN28352) and this Tau PET substudy, such that the total research-related radiation dose to the participant in any given year would exceed the limits set forth in the U.S. Code of Federal Regulations (CFR) Title 21 Section 361.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
[^18F]GTP1 in Mutation Carriers: Placebo	[^18F]GTP1	Mutation-carrying participants receiving placebo in the main study NCT01998841 (GN28352) will receive up to three IV injections of \[\^18F\]GTP1 and will undergo a tau PET scan after each IV injection of \[\^18F\]GTP1.
[^18F]GTP1 in Non-carriers of Mutation: Placebo	[^18F]GTP1	Non-carriers of the mutation receiving placebo in the main study NCT01998841 (GN28352) will receive up to three IV injections of \[\^18F\]GTP1 and will undergo a tau PET scan after each IV injection of \[\^18F\]GTP1.
[^18F]GTP1 in Mutation Carriers: Placebo	Placebo	Mutation-carrying participants receiving placebo in the main study NCT01998841 (GN28352) will receive up to three IV injections of \[\^18F\]GTP1 and will undergo a tau PET scan after each IV injection of \[\^18F\]GTP1.
[^18F]GTP1 in Non-carriers of Mutation: Placebo	Placebo	Non-carriers of the mutation receiving placebo in the main study NCT01998841 (GN28352) will receive up to three IV injections of \[\^18F\]GTP1 and will undergo a tau PET scan after each IV injection of \[\^18F\]GTP1.
[^18F]GTP1 in Mutation Carriers: Crenezumab	Crenezumab	Mutation-carrying participants receiving crenezumab in the main study NCT01998841 (GN28352) will receive up to three IV injections of \[\^18F\]GTP1 and will undergo a tau PET scan after each IV injection of \[\^18F\]GTP1.
[^18F]GTP1 in Mutation Carriers: Crenezumab	[^18F]GTP1	Mutation-carrying participants receiving crenezumab in the main study NCT01998841 (GN28352) will receive up to three IV injections of \[\^18F\]GTP1 and will undergo a tau PET scan after each IV injection of \[\^18F\]GTP1.

Primary Outcome Measures

Name	Time	Method
Annualized Rate of Change in Tau Burden	Baseline up to Week 149	Tau is a protein that accumulates in Alzheimer's disease and damages brain cells including those essential for learning and memory. The effect of crenezumab on tau burden was assessed using \[18F\]GTP1 Tau PET. The annualized rate of change in tau burden from the first \[18F\]GTP1 scan of the standardized uptake ratio (SUVR) in the entorhinal cortex (Braak Stage 1) with an inferior cerebellum reference region was analyzed using a random coefficient regression model (RCRM). Braak staging classifies the degree of pathology in Alzheimer's disease. Braak stages 1 and 2 are used when neurofibrillary tangle involvement is confined mainly to the transentorhinal region of the brain, stages 3 and 4 when there is also involvement of limbic regions such as the hippocampus, and 5 and 6 when there is extensive neocortical involvement.

Secondary Outcome Measures